Abstract: Postmortem human brain tissue is essential for studies of the pathobiology and causes of Parkinson's disease (PD). The chief goal of the Clinical &Neuropathology Core (Core D) is to obtain and provide well-characterized postmortem human brain tissue for investigations of the etiology and basic mechanisms of Parkinson's disease (PD). These tissues are necessary to validate the hypotheses and observations generated by the studies of cellular and molecular biology and experimental animal models proposed in Projects 1-3. Core D clinical assessment protocols in concert with its neuropathological analyses and laboratory facilities enable acquisition of clinical data, brain tissue, and genetic material from the same subject and serve as powerful resources for validating findings from the Center's cellular and transgenic model studies. Accordingly, the staff of Core D recruits and follows clinically patients with PD and related disorders, as well as controls. These subjects give consent for eventual autopsy and brain donation and are enrolled in a prospective autopsy cohort. At death, the Core arranges and performs autopsies and provides neuropathological diagnoses in these subjects. Postmortem tissues are prepared and archived both for diagnostic and research purposes by the Brain Resource Center (BRC). The BRC serves as a repository of fixed and frozen brain tissues prepared for research including cases of PD, other Lewy body diseases, and normal and diseased controls. Core D also maintains and staffs histology, immunocytochemistry and stereology laboratories to support and facilitate the morphological assessment of human and experimental mouse models relevant to the studies of PD delineated in Projects 1-3. Finally, Core D provides the fundamental infrastructure to facilitate independently funded clinical and clinicopathological investigations of PD at JHMI and collaborating institutions and trains basic investigators and clinical neuroscientists in clinical and neuropathology issues relevant to PD. RELEVANCE (See instructions): The Clinical and Neuropathology Core serves as a resource for all of the research projects in the PD Center. Its main goal is to conduct clinical assessments and postmortem examination of patients with PD. The Core provides postmortem brain tissues to all of the Projects in the Hopkins PD Center and to investigators in other Udall Centers. The availability of these tissue samples is a critical step in the investigation of the causes and underlying mechanisms of PD.